Autoinjector

ABSTRACT

Described is an autoinjector ( 1 ) comprising a case ( 2 ), a syringe carrier ( 8 ) slidably disposed within the case ( 2 ) and adapted to hold a syringe ( 3 ) including a stopper ( 6 ), a plunger ( 12 ) slidably disposed within the syringe carrier ( 8 ) and adapted to apply a force on the stopper ( 6 ), and a drive spring ( 10 ) disposed within the plunger ( 12 ) and biasing the plunger ( 12 ) relative to the syringe carrier ( 8 ).

TECHNICAL FIELD

The invention relates to an autoinjector.

BACKGROUND OF THE INVENTION

Administering an injection is a process which presents a number of risksand challenges for users and healthcare professionals, both mental andphysical. Injection devices typically fall into two categories—manualdevices and autoinjectors. In a conventional manual device, manual forceis required to drive a medicament through a needle. This is typicallydone by some form of button/plunger that has to be continuously pressedduring the injection. There are numerous disadvantages associated withthis approach. For example, if the button/plunger is releasedprematurely, the injection will stop and may not deliver an intendeddose. Further, the force required to push the button/plunger may be toohigh (e.g., if the user is elderly or a child). And, aligning theinjection device, administering the injection and keeping the injectiondevice still during the injection may require dexterity which somepatients (e.g., elderly patients, children, arthritic patients, etc.)may not have.

Autoinjector devices aim to make self-injection easier for patients. Aconventional autoinjector may provide the force for administering theinjection by a spring, and trigger button or other mechanism may be usedto activate the injection. Autoinjectors may be single-use or reusabledevices.

There remains a need for an improved autoinjector.

SUMMARY OF THE INVENTION

It is an object of the present invention to provide an improvedautoinjector.

In an exemplary embodiment, an autoinjector according to the presentinvention comprises a case, a syringe carrier slidably disposed withinthe case and adapted to hold a syringe including a stopper, a plungerslidably disposed within the syringe carrier and adapted to apply aforce on the stopper, and a drive spring disposed within the plunger andbiasing the plunger relative to the syringe carrier.

In an exemplary embodiment, the autoinjector further comprises a needleshroud slidably disposed within the case. The needle shroud istelescopically arranged over the syringe carrier. In an exemplaryembodiment, the autoinjector further comprises detent mechanism adaptedto couple the needle shroud to the syringe carrier and adapted to couplethe needle shroud to the case. The detent mechanism comprises aresilient shroud beam on the needle shroud having a shroud bossreleasably engaging a carrier opening in the syringe carrier. The caseincludes a proximal case boss abutting the shroud boss when the needleshroud is in a first extended position.

In an exemplary embodiment, the autoinjector further comprises a plungerrelease mechanism adapted to releasably couple the plunger to thesyringe carrier. The plunger release mechanism comprises a resilientcarrier beam on the syringe carrier having a carrier boss releasablyengaging a plunger opening in the plunger.

In an exemplary embodiment, the autoinjector further comprises a collarslidably arranged on the syringe carrier, and a control spring applyinga biasing force to the collar. The collar includes a resilient collarbeam having a collar boss adapted to releasably engage a step on thesyringe carrier. The collar abuts the carrier boss when the needleshroud is in the first extended position. The collar, the needle shroudand the syringe carrier are moved proximally relative to the case whenthe needle shroud is moved from the first extended position to a firstretracted position. A proximal end of the syringe carrier abuts aproximal end of the case when the needle shroud is in the firstretracted position to provide a feedback. The shroud boss is proximal ofthe proximal case boss when the needle shroud is in the first retractedposition. The syringe carrier is advanced distally when the needleshroud is in a second retracted position proximal of the first retractedposition, and the shroud boss disengages the carrier opening. When theshroud boss disengages the carrier opening, the collar pushes thesyringe carrier distally until the syringe carrier abuts a front stop inthe case and the collar disengages the syringe carrier under the biasingforce of the control spring and pushes the needle shroud into a secondextended position relative to the case. When the collar disengages thesyringe carrier, the carrier boss disengages the plunger opening torelease the plunger. The shroud boss abuts a distal case boss when theneedle shroud is in the second extended position.

In an exemplary embodiment, the syringe carrier with the integrateddrive spring allows for employing a strong drive spring without anyimpact on the user when triggering the autoinjector or during needleinsertion since these actions are achieved or opposed by the controlspring which can be specified considerably weaker than the drive spring.This allows for delivering highly viscous medicaments.

In an exemplary embodiment, releasing the drive spring upon the needlereaching an insertion depth avoids a so called wet injection, i.e.medicament leaking out of the needle which is a problem in conventionalart autoinjectors, where both needle insertion and injection areachieved by pushing on the stopper.

In an exemplary embodiment, the autoinjector has a particularly low partcount compared to most conventional autoinjectors thus reducingmanufacturing costs. The arrangement with separate control spring foradvancing the syringe and the needle shroud and a drive spring for fluidinjection allows for using one design for different viscosity liquids byjust changing the drive spring, and for different volumes just bychanging the length of the plunger. This may be an advantage overconventional designs where the drive spring also serves for needleinsertion and/or for advancing a shroud.

Further scope of applicability of the present invention will becomeapparent from the detailed description given hereinafter. However, itshould be understood that the detailed description and specificexamples, while indicating preferred embodiments of the invention, aregiven by way of illustration only, since various changes andmodifications within the spirit and scope of the invention will becomeapparent to those skilled in the art from this detailed description.

BRIEF DESCRIPTION OF THE DRAWINGS

The present invention will become more fully understood from thedetailed description given hereinbelow and the accompanying drawingswhich are given by way of illustration only, and thus, are not limitiveof the present invention, and wherein:

FIG. 1A is a perspective view of an exemplary embodiment of anautoinjector according to the present invention prior to use,

FIG. 1B is a longitudinal section of an exemplary embodiment of anautoinjector according to the present invention prior to use,

FIG. 1C is a different longitudinal section of an exemplary embodimentof an autoinjector according to the present invention prior to use,

FIG. 2A is a perspective view of an exemplary embodiment of anautoinjector according to the present invention during use,

FIG. 2B is a longitudinal section of an exemplary embodiment of anautoinjector according to the present invention during use,

FIG. 2C is a different longitudinal section of an exemplary embodimentof an autoinjector according to the present invention during use,

FIG. 3A is a perspective view of an exemplary embodiment of anautoinjector according to the present invention during use,

FIG. 3B is a longitudinal section of an exemplary embodiment of anautoinjector according to the present invention during use,

FIG. 3C is a different longitudinal section of an exemplary embodimentof an autoinjector according to the present invention during use,

FIG. 4A is a perspective view of an exemplary embodiment of anautoinjector according to the present invention during use,

FIG. 4B is a longitudinal section of an exemplary embodiment of anautoinjector according to the present invention during use,

FIG. 4C is a different longitudinal section of an exemplary embodimentof an autoinjector according to the present invention during use,

FIG. 5A is a perspective view of an exemplary embodiment of anautoinjector according to the present invention after use,

FIG. 5B is a longitudinal section of an exemplary embodiment of anautoinjector according to the present invention after use, and

FIG. 5C is a different longitudinal section of an exemplary embodimentof an autoinjector according to the present invention after use.

Corresponding parts are marked with the same reference symbols in allfigures.

DETAILED DESCRIPTION

FIG. 1A is a perspective view of an exemplary embodiment of anautoinjector 1 comprising a case 2 and a cap 11 prior to use. FIGS. 1Band 1C are longitudinal sections of the autoinjector 1 prior to use.

In an exemplary embodiment, the autoinjector 1 comprises a case 2including a distal case 2.1 and a proximal case 2.2 which are coupledduring assembly. A cap 11 is removably coupled to a distal end of thecase 2. The case 2 comprises a viewing window 2.7, which may be a holeor a transparent portion of the case 2.

The case 2 is adapted to hold a syringe 3 containing a medicament. Thesyringe 3 may be a pre-filled syringe and have a needle 4 arranged at adistal end. In another exemplary embodiment, the syringe 3 may be amedicament cartridge adapted to removably receive the needle 4 (e.g., bysnap-fit, friction, threads, etc.). A protective needle sheath 5 may beremovably attached to the needle 4. A stopper 6 is arranged for sealingthe syringe 3 proximally and for displacing a liquid medicament Mcontained in the syringe 3 through the needle 4.

A needle shroud 7 is telescoped within the case 2 and movable between anextended position and a retracted position. The needle shroud 7 isbiased relative to the case 2 toward the extended position by a controlspring 9.

In an exemplary embodiment, the syringe 3 may be held in a syringecarrier 8, which is slidably arranged within the case 2. The syringecarrier 8 may include a distal portion adapted to hold the syringe 3 anda proximal portion adapted to retain a plunger 12. A drive spring 10,e.g., a compression spring, may be grounded proximally on a proximal endof the syringe carrier 8 and distally on a distal end of the plunger 12.In an exemplary embodiment, the plunger 12 is telescopically coupled tothe proximal portion of the syringe carrier 8, and the drive spring 10is arranged within the plunger 12 and biases the plunger 12 distally.

In an exemplary embodiment, the drive spring 10 is arranged within aproximal part 8.1 of the syringe carrier 8. A plunger 12 serves forforwarding the force of the drive spring 10 to the stopper 6. In anexemplary embodiment the plunger 12 is hollow and telescoped within theproximal part 8.1 of the syringe carrier 8 wherein the drive spring 10is arranged within the plunger 12 biasing the plunger 12 in the distaldirection D against the syringe carrier 8.

In an exemplary embodiment, a detent mechanism 14 is provided toinitiate automated needle insertion. The detent mechanism 14 also locksthe needle shroud 7 after autoinjector 1 has been removed from theinjection site in an extended position.

In an exemplary embodiment, the detent mechanism 14 comprises at leastone shroud boss 7.1 adapted to engage in a carrier opening 8.6 withinthe syringe carrier 8 for locking the needle shroud 7 to the syringecarrier 8. At least one surface of the shroud boss 7.1 and the carrieropening 8.6 may be ramped to reduce a force necessary to displace theneedle shroud 7 from the extended position to the retracted positionagainst the biasing force of the control spring 9. When the force on theneedle shroud 7 overcomes the biasing force of the control spring 9, theshroud boss 7.1 abuts the carrier opening 8.6 and deflects radailly viaa compliant beam 7.2 coupled to the shroud boss 7.1, disengaging theneedle shroud 7 from the syringe carrier 8. When the needle shroud 7 isin a first extended position FEP relative to the case 2 (as shown inFIGS. 1B and 1C), the shroud boss 7.1 radially abuts a radial case boss2.9, which prevents the needle shroud 7 from disengaging the syringecarrier 8 when the needle shroud 7 is in the first extended positionFEP. An axial case boss 2.10 is adapted to distally abut the shroud boss7.1 such that the needle shroud 7 cannot be moved distally beyond thefirst extended position FEP prior to use. At least one of the surfacesof the shroud boss 7.1 and the axial case boss 2.10 may be ramped suchthat if an axial force directed in the distal direction D is applied tothe needle shroud 7 relative the case 2, the needle shroud 7 moves inthe distal direction D relative the case 2 and the shroud boss 7.1 isradially inwardly deflected via the resilient beam 7.2 around the axialcase boss 2.10. Prior to use, the shroud boss 7.1 is prevented fromdeflecting radially inward by the presence of the syringe carrier 8.Thus, prior to use the needle shroud 7.1 does not disengage the case 2.

In an exemplary embodiment, a plunger release mechanism 15 is arrangedfor preventing release of the plunger 12 prior to the needle 4 reachingan insertion depth and for releasing the plunger 12 once the needle 4reaches its insertion depth. In an exemplary embodiment, the plungerrelease mechanism 15 comprises: one or more compliant beams 8.3 with arespective first boss 8.4 arranged on the syringe carrier 8, arespective first opening 12.1 laterally arranged in the plunger 12 forengaging the first boss 8.4, a collar 16 slidably arranged within thecase 2 and over the syringe carrier 8. When the needle shroud 7 is inthe first extended position FEP, the collar 16 abuts the first boss 8.4,preventing it from disengaging the first opening 12.1. As describedfurther below, as the needle 4 reaches its insertion depth, the collar16 moves axially away from the first boss 8.4, so that the first boss8.4 may deflect via the beam 8.3 and disengage from the first opening12.1. The syringe carrier 8 is then disengaged from the plunger 12. Atleast surface of the first boss 8.4 and the first opening 12.1 may beramped to reduce a force necessary to disengage the first boss 8.4 fromthe first opening 12.1.

In an exemplary embodiment, a control mechanism 21 (shown in FIG. 3B) isarranged for selectively coupling the control spring 9 to the syringecarrier 8 or to the needle shroud 7 for advancing either in the distaldirection D or opposing movement thereof in the proximal direction P. Inan exemplary embodiment, the collar 16 may be a component of the controlmechanism 21. The control spring 9 is proximally grounded in the case 2and distally bears against the collar 16 which is movable axially withrespect to the case 2 and arranged over the syringe carrier 8. Thecollar 16 comprises at least one collar boss 16.1 adapted to be engagedto a step 8.5 in the carrier 8. At least one of the mating surfaces ofthe carrier boss 16.1 and the step 8.5 may be ramped to reduce a forcenecessary to deflect the collar boss 16.1 radially via a compliantcollar beam 16.2 when it abuts the step 8.5. Once assembled, the collarboss 16.1 is prevented from deflecting radially by a narrow section 2.4in the case 2. A wide section 2.5 is arranged distally from the narrowsection 2.4. Upon axial movement of the syringe carrier 8 and the collar16 in the distal direction D, the carrier boss 16.1 can deflect radiallywhen the collar 16 enters the wide section 2.5 and disengage the collar16 from the syringe carrier 8 under force from the control spring 9.

In an exemplary embodiment, prior to use the control spring 9 iscompressed between the case 2 and the collar 16. The control mechanism21 couples the collar 16 to the syringe carrier 8 which is in turncoupled to the case 2 by the detent mechanism 14.

A exemplary embodiment of a sequence of operation of the autoinjector 1is as follows:

Prior to use, the autoinjector 1 is in the state as illustrated in FIGS.1A to 1C. If applicable, the user removes the autoinjector 1 from apackaging. The medicament M may be viewed through the viewing window2.7. The cap 11 is removed from the case 2 by pulling the cap 11 in thedistal direction D. The cap 11 is coupled to the protective needlesheath 5, and thus removing the cap 11 also removes the protectiveneedle sheath 5. Prior to use, the needle shroud 7 is in the firstextended position FEP protruding from the case 2 in the distal directionD. The first extended position FEP is defined by the detent mechanism14, i.e. by the engagement of the shroud boss 7.1 in the carrier opening8.6 of the syringe carrier 8 and abutment of the shroud boss 7.1 againstthe axial case boss 2.10 to prevent it from disengaging the carrieropening 8.6.

FIGS. 2A-C are perspective views of the autoinjector 1 being pressedagainst an injection site. When the autoinjector 1 is pressed againstthe injection site, the needle shroud 7 moves from the first extendedposition FEP toward a first retracted position FRP relative to the case2. Because the needle shroud 7 is coupled to the syringe carrier 8 bythe detent mechanism 14 (by the shroud boss 7.1 engagement with thecarrier opening 8.6), the syringe carrier 8 (and the syringe 3 therein)are retracted relative to the case 2 such that the needle 4 is notexposed. Because the collar 16 is coupled to the syringe carrier 8 (bythe collar boss 16.1 abutting the step 8.5), the collar 16 is moved withthe syringe carrier 8 in the proximal direction P against the force ofthe control spring 9.

When the needle shroud 7 has reached the first retracted position FRP,the proximal end 8.1 of the syringe carrier 8 may contact (or nearlycontact) a proximal end 2.11 of the case 2. The contact between thesyringe carrier 8 and the case 2 (and/or the increased resistanceprovided by the control spring 9) may provide a tactile feedback thatfurther depression of the needle shroud 7 will activate the autoinjector1. In the first retracted position FRP, the shroud boss 7.1 is proximalof the case boss 2.9 such that the shroud boss 7.1 no longer abuts thecase boss 2.9. However, in an exemplary embodiment, the biasing force ofthe control spring 9 is less than the force required to deflect theshroud boss 7.1 out of the carrier opening 8.6. Thus, if the needleshroud 7 is not further depressed and the autoinjector 1 is removed fromthe injection site (or axial force is no longer applied to theautoinjector 1), the needle shroud 7 will re-extend into the firstextended position FEP and the autoinjector 1 will return to its initialstate.

FIGS. 3A-C are perspective views of the autoinjector 1 being pressedagainst an injection site. As the user continues to depress the needleshroud 7 into a second retracted position SRP, an increase in resistanceis experienced as the case 2 advances the syringe carrier 8 in thedistal direction D relative to the needle shroud 7 through contact ofthe proximal ends 2.11, 8.1 of the case 2 and the syringe carrier 8. Asthe shroud boss 7.1 is no longer radially supported by the case boss2.9, as the case 2 is advanced in the distal direction D, the shroudboss 7.1 is deflected radially when it abuts the carrier opening 8.6,causing the syringe carrier 8 to disengage from the needle shroud 7.

FIGS. 4A-C are perspective views of the autoinjector 1 being pressedagainst an injection site. When the shroud boss 7.1 disengages thecarrier opening 8.6, the syringe carrier 8 is decoupled from the needleshroud 7. The control spring 9 applies the biasing force to the collar16, and the collar boss 16.1 pushes the step 8.5 on the syringe carrier8 to drive the syringe carrier 8 (and the syringe 3) in the distaldirection D. When the syringe carrier 8 abuts a front stop 2.8 in thecase 2, the needle 4 protrudes beyond the distal end of the case 2 andis inserted into the injection site. The collar 16 has been advanced inthe distal direction D to such an extent, that the collar boss 16.1 isno longer supported by the narrow section 2.4 but has reached the widesection 2.5 of the case 2. The control spring 9 continues advancing thecollar 16 and due to the syringe carrier 8 having abutted the front stop2.8, the collar boss 16.1 is deflected radially, disengaging the collar16 from the syringe carrier 8. The collar 16 advances further under theforce of the control spring 9 until it abuts the needle shroud 7.

As the collar 16 advances, it is distal of the first boss 8.4 on thesyringe carrier 8 so as to allow radially deflection of the first boss8.4 due to its ramped engagement to the first opening 12.1 under loadfrom the drive spring 10. The plunger 12 is thus released and advancedby the drive spring 10 displacing the stopper 6 within the syringe 3 andejecting the medicament M through the needle 4. The release of theplunger release mechanism 15 may provide an audible and/or tactilefeedback to the user. The progress of the delivery of the medicament Mcan be observed through the viewing window 2.7 by examining the movementof the plunger 12. The plunger 12 (which may be a contrasting color tothe case 2) is visible in the viewing window 2.7, providing visualfeedback about whether or not the autoinjector 1 has been used.

If the user removes the autoinjector 1 from the injection site at anytime after the needle 4 having reached insertion depth, the needleshroud 7 moves in the distal direction D, because it is abutted by thecollar 16 which is driven by the control spring 9.

FIGS. 5A-C are perspective views of the autoinjector 1 after it isremoved from the injection site. As the needle shroud 7 advances in thedistal direction D under the force of the control spring 9, the shroudboss 7.1 is deflected radially by the axial case boss 2.10 since thesyringe carrier 8 has been moved in the distal direction D during needleinsertion and does not abut the shroud boss 7.1. The shroud boss 7.1hence deflects around the case boss 2.10, and then returns to anon-deflected position when it is distal of the case boss 2.10. Theshroud boss 7.1 abuts a ramped stop 8.7 on the syringe carrier 8 whichresolves the remaining axial force of the control spring 9 and arreststhe needle shroud's 7 extension. The needle shroud 7 is now in a secondextended position SEP extending further from the case 2 than in thefirst extended position FEP and the extended needle 4 is hidden fromview and finger access within the needle shroud 7.

Any attempt to displace the needle shroud 7 in the proximal direction Prelative to the case 2 from the second extended position SEP isprevented, because the shroud boss 7.1 abuts a distal end of the caseboss 2.10.

In another exemplary embodiment, an opening may be arranged in theproximal end 2.11 of the case 2 allowing the proximal part 8.1 of thesyringe carrier 8 to protrude proximally from the case 2 and serve as atrigger button (not shown). In this exemplary embodiment, the detentmechanism 14 prevents release of the trigger button prior to depressionof the needle shroud 7 into the retracted position RP. The needle shroud7 may be fully depressed into the second retracted position SRP therebyextending the proximal part 8.1 of the syringe carrier 8 from the case 2which may then be depressed to start an injection. If the trigger buttonis not depressed at this point, the needle shroud 7 can re-extend intothe first extended position FEP and the autoinjector 1 can return to itsinitial state. If the trigger button is depressed, it may be locked tothe case in the depressed position to provide a visual indication thatthe autoinjector 1 has been used.

After full depression of the needle shroud 7 into the second retractedposition SRP, the shroud boss 7.1 is no longer supported by the caseboss 2.9. The trigger button, e.g., the proximal end 8.1 of the syringecarrier 8 protruding proximally from the case 2 can now be depressedthereby radially outwardly deflecting the shroud boss 7.1 out ofengagement with the carrier opening 8.6 due to their ramped engagement.The syringe carrier 8 is thus decoupled from the needle shroud 7 and thecontrol spring 9, coupled to the syringe carrier 8 through the controlmechanism 21, advances the syringe carrier 8 in the distal direction Dextending the needle 4 from the case 2 in the distal direction D. Thelength of the syringe carrier 8 and the case 2 may be such that theproximal end 8.1 of the syringe carrier 8 is flush with the proximal end2.11 of the case 2 once the needle 4 reaches its insertion depth.

The term “drug” or “medicament”, as used herein, means a pharmaceuticalformulation containing at least one pharmaceutically active compound,

wherein in one embodiment the pharmaceutically active compound has amolecular weight up to 1500 Da and/or is a peptide, a proteine, apolysaccharide, a vaccine, a DNA, a RNA, an enzyme, an antibody or afragment thereof, a hormone or an oligonucleotide, or a mixture of theabove-mentioned pharmaceutically active compound,

wherein in a further embodiment the pharmaceutically active compound isuseful for the treatment and/or prophylaxis of diabetes mellitus orcomplications associated with diabetes mellitus such as diabeticretinopathy, thromboembolism disorders such as deep vein or pulmonarythromboembolism, acute coronary syndrome (ACS), angina, myocardialinfarction, cancer, macular degeneration, inflammation, hay fever,atherosclerosis and/or rheumatoid arthritis,

wherein in a further embodiment the pharmaceutically active compoundcomprises at least one peptide for the treatment and/or prophylaxis ofdiabetes mellitus or complications associated with diabetes mellitussuch as diabetic retinopathy,

wherein in a further embodiment the pharmaceutically active compoundcomprises at least one human insulin or a human insulin analogue orderivative, glucagon-like peptide (GLP-1) or an analogue or derivativethereof, or exendin-3 or exendin-4 or an analogue or derivative ofexendin-3 or exendin-4.

Insulin analogues are for example Gly(A21), Arg(B31), Arg(B32) humaninsulin; Lys(B3), Glu(B29) human insulin; Lys(B28), Pro(B29) humaninsulin; Asp(B28) human insulin; human insulin, wherein proline inposition B28 is replaced by Asp, Lys, Leu, Val or Ala and wherein inposition B29 Lys may be replaced by Pro; Ala(B26) human insulin;Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) humaninsulin.

Insulin derivates are for example B29-N-myristoyl-des(B30) humaninsulin; B29-N-palmitoyl-des(B30) human insulin; B29-N-myristoyl humaninsulin; B29-N-palmitoyl human insulin; B28-N-myristoyl LysB28ProB29human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin;B30-N-myristoyl-ThrB29LysB30 human insulin; B30-N-palmitoyl-ThrB29LysB30human insulin; B29-N-(N-palmitoyl-Y-glutamyl)-des(B30) human insulin;B29-N-(N-lithocholyl-Y-glutamyl)-des(B30) human insulin;B29-N-(ω-carboxyheptadecanoyl)-des(B30) human insulin andB29-N-(ω-carboxyheptadecanoyl) human insulin.

Exendin-4 for example means Exendin-4(1-39), a peptide of the sequenceH-His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Lsn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2.

Exendin-4 derivatives are for example selected from the following listof compounds:

H-(Lys)4-des Pro36, des Pro37 Exendin-4(1-39)-NH2,

H-(Lys)5-des Pro36, des Pro37 Exendin-4(1-39)-NH2,

des Pro36 Exendin-4(1-39),

des Pro36 [Asp28] Exendin-4(1-39),

des Pro36 [IsoAsp28] Exendin-4(1-39),

des Pro36 [Met(O)14, Asp28] Exendin-4(1-39),

des Pro36 [Met(O)14, IsoAsp28] Exendin-4(1-39),

des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39),

des Pro36 [Trp(O2)25, IsoAsp28] Exendin-4(1-39),

des Pro36 [Met(O)14 Trp(02)25, Asp28] Exendin-4(1-39),

des Pro36 [Met(O)14 Trp(O2)25, IsoAsp28] Exendin-4(1-39); or

des Pro36 [Asp28] Exendin-4(1-39),

des Pro36 [IsoAsp28] Exendin-4(1-39),

des Pro36 [Met(O)14, Asp28] Exendin-4(1-39),

des Pro36 [Met(O)14, IsoAsp28] Exendin-4(1-39),

des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39),

des Pro36 [Trp(O2)25, IsoAsp28] Exendin-4(1-39),

des Pro36 [Met(O)14 Trp(O2)25, Asp28] Exendin-4(1-39),

des Pro36 [Met(O)14 Trp(O2)25, IsoAsp28] Exendin-4(1-39),

wherein the group -Lys6-NH2 may be bound to the C-terminus of theExendin-4 derivative;

or an Exendin-4 derivative of the sequence

des Pro36 Exendin-4(1-39)-Lys6-NH2 (AVE0010),

H-(Lys)6-des Pro36 [Asp28] Exendin-4(1-39)-Lys6-NH2,

des Asp28 Pro36, Pro37, Pro38Exendin-4(1-39)-NH2,

H-(Lys)6-des Pro36, Pro38 [Asp28] Exendin-4(1-39)-NH2,

H-Asn-(Glu)5des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-NH2,

des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39)-Lys6-NH2,

H-des Asp28 Pro36, Pro37, Pro38 [Trp(O2)25] Exendin-4(1-39)-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]Exendin-4(1-39)-NH2,

des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36 [Met(O)14, Asp28] Exendin-4(1-39)-Lys6-NH2,

des Met(O)14 Asp28 Pro36, Pro37, Pro38 Exendin-4(1-39)-NH2,

H-(Lys)6-desPro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Asp28]Exendin-4(1-39)-NH2,

des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-Asn-(Glu)5 des Pro36, Pro37, Pro38 [Met(O)14, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-Lys6-des Pro36 [Met(O)14, Trp(O2)25, Asp28] Exendin-4(1-39)-Lys6-NH2,

H-des Asp28 Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25]Exendin-4(1-39)-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]Exendin-4(1-39)-NH2,

des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]Exendin-4(S1-39)-(Lys)6-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]Exendin-4(1-39)-(Lys)6-NH2;

or a pharmaceutically acceptable salt or solvate of any one of theafore-mentioned Exendin-4 derivative.

Hormones are for example hypophysis hormones or hypothalamus hormones orregulatory active peptides and their antagonists as listed in RoteListe, ed. 2008, Chapter 50, such as Gonadotropine (Follitropin,Lutropin, Choriongonadotropin, Menotropin), Somatropine (Somatropin),Desmopressin, Terlipressin, Gonadorelin, Triptorelin, Leuprorelin,Buserelin, Nafarelin, Goserelin.

A polysaccharide is for example a glucosaminoglycane, a hyaluronic acid,a heparin, a low molecular weight heparin or an ultra low molecularweight heparin or a derivative thereof, or a sulphated, e.g. apoly-sulphated form of the above-mentioned polysaccharides, and/or apharmaceutically acceptable salt thereof. An example of apharmaceutically acceptable salt of a poly-sulphated low molecularweight heparin is enoxaparin sodium.

Antibodies are globular plasma proteins (−150 kDa) that are also knownas immunoglobulins which share a basic structure. As they have sugarchains added to amino acid residues, they are glycoproteins. The basicfunctional unit of each antibody is an immunoglobulin (Ig) monomer(containing only one Ig unit); secreted antibodies can also be dimericwith two Ig units as with IgA, tetrameric with four Ig units liketeleost fish IgM, or pentameric with five Ig units, like mammalian IgM.

The Ig monomer is a “Y”-shaped molecule that consists of fourpolypeptide chains; two identical heavy chains and two identical lightchains connected by disulfide bonds between cysteine residues. Eachheavy chain is about 440 amino acids long; each light chain is about 220amino acids long. Heavy and light chains each contain intrachaindisulfide bonds which stabilize their folding. Each chain is composed ofstructural domains called Ig domains. These domains contain about 70-110amino acids and are classified into different categories (for example,variable or V, and constant or C) according to their size and function.They have a characteristic immunoglobulin fold in which two β sheetscreate a “sandwich” shape, held together by interactions betweenconserved cysteines and other charged amino acids.

There are five types of mammalian Ig heavy chain denoted by α, δ, ε, γ,and μ. The type of heavy chain present defines the isotype of antibody;these chains are found in IgA, IgD, IgE, IgG, and IgM antibodies,respectively.

Distinct heavy chains differ in size and composition; a and y containapproximately 450 amino acids and 6 approximately 500 amino acids, whilep and c have approximately 550 amino acids. Each heavy chain has tworegions, the constant region (C_(H)) and the variable region (V_(H)). Inone species, the constant region is essentially identical in allantibodies of the same isotype, but differs in antibodies of differentisotypes. Heavy chains γ, α and δ have a constant region composed ofthree tandem Ig domains, and a hinge region for added flexibility; heavychains p and c have a constant region composed of four immunoglobulindomains. The variable region of the heavy chain differs in antibodiesproduced by different B cells, but is the same for all antibodiesproduced by a single B cell or B cell clone. The variable region of eachheavy chain is approximately 110 amino acids long and is composed of asingle Ig domain.

In mammals, there are two types of immunoglobulin light chain denoted byλ and κ. A light chain has two successive domains: one constant domain(CL) and one variable domain (VL). The approximate length of a lightchain is 211 to 217 amino acids. Each antibody contains two light chainsthat are always identical; only one type of light chain, κ or λ, ispresent per antibody in mammals.

Although the general structure of all antibodies is very similar, theunique property of a given antibody is determined by the variable (V)regions, as detailed above. More specifically, variable loops, threeeach the light (VL) and three on the heavy (VH) chain, are responsiblefor binding to the antigen, i.e. for its antigen specificity. Theseloops are referred to as the Complementarity Determining Regions (CDRs).Because CDRs from both VH and VL domains contribute to theantigen-binding site, it is the combination of the heavy and the lightchains, and not either alone, that determines the final antigenspecificity.

An “antibody fragment” contains at least one antigen binding fragment asdefined above, and exhibits essentially the same function andspecificity as the complete antibody of which the fragment is derivedfrom. Limited proteolytic digestion with papain cleaves the Ig prototypeinto three fragments. Two identical amino terminal fragments, eachcontaining one entire L chain and about half an H chain, are the antigenbinding fragments (Fab). The third fragment, similar in size butcontaining the carboxyl terminal half of both heavy chains with theirinterchain disulfide bond, is the crystalizable fragment (Fc). The Fccontains carbohydrates, complement-binding, and FcR-binding sites.Limited pepsin digestion yields a single F(ab′)2 fragment containingboth Fab pieces and the hinge region, including the H-H interchaindisulfide bond. F(ab′)2 is divalent for antigen binding. The disulfidebond of F(ab′)2 may be cleaved in order to obtain Fab′. Moreover, thevariable regions of the heavy and light chains can be fused together toform a single chain variable fragment (scFv).

Pharmaceutically acceptable salts are for example acid addition saltsand basic salts.

Acid addition salts are e.g. HCl or HBr salts. Basic salts are e.g.salts having a cation selected from alkali or alkaline, e.g. Na+, or K+,or Ca2+, or an ammonium ion N+(R1)(R2)(R3)(R4), wherein R1 to R4independently of each other mean: hydrogen, an optionally substitutedC1-C6-alkyl group, an optionally substituted C2-C6-alkenyl group, anoptionally substituted C6-C10-aryl group, or an optionally substitutedC6-C10-heteroaryl group. Further examples of pharmaceutically acceptablesalts are described in “Remington's Pharmaceutical Sciences” 17. ed.Alfonso R. Gennaro (Ed.), Mark Publishing Company, Easton, Pa., U.S.A.,1985 and in Encyclopedia of Pharmaceutical Technology.

Pharmaceutically acceptable solvates are for example hydrates.

Those of skill in the art will understand that modifications (additionsand/or removals) of various components of the apparatuses, methodsand/or systems and embodiments described herein may be made withoutdeparting from the full scope and spirit of the present invention, whichencompass such modifications and any and all equivalents thereof.

1. An autoinjector (1) comprising: a case (2) a syringe carrier (8) slidably disposed within the case (2), the syringe carrier (8) adapted to hold a syringe (3) including a stopper (6); a plunger (12) slidably disposed within the syringe carrier (8), the plunger (12) adapted to apply a force on the stopper (6); a drive spring (10) disposed within the plunger (12) and biasing the plunger (12) relative to the syringe carrier (8); a needle shroud (7) slidably disposed within the case (2), the needle shroud (7) telescopically arranged over the syringe carrier (8); and a detent mechanism (14) adapted to (i) couple the needle shroud (7) to the syringe carrier (8) and (ii) adapted to couple the needle shroud (7) to the case (2).
 2. The autoinjector (1) according to claim 1, wherein the detent mechanism (14) comprises a resilient shroud beam (7.2) on the needle shroud (7) having a shroud boss (7.1) releasably engaging a carrier opening (8.6) in the syringe carrier (8).
 3. The autoinjector (1) according to claim 2, wherein the case (2) includes a proximal case boss (2.9) abutting the shroud boss (7.1) when the needle shroud (7) is in a first extended position (FEP).
 4. The autoinjector (1) according to any one of the preceding claims, further comprising: a plunger release mechanism (15) adapted to releasably couple the plunger (12) to the syringe carrier (8).
 5. The autoinjector (1) according to claim 4, wherein the plunger release mechanism (15) comprises a resilient carrier beam (8.3) on the syringe carrier (8) having a carrier boss (8.4) releasably engaging a plunger opening (12.1) in the plunger (12).
 6. The autoinjector (1) according to any one of the preceding claims, further comprising: a collar (16) slidably arranged on the syringe carrier (8); and a control spring (9) applying a biasing force to the collar (16).
 7. The autoinjector (1) according to claim 6, wherein the collar (16) includes a resilient collar beam (16.2) having a collar boss (16.1) adapted to releasably engage a step (8.5) on the syringe carrier (8).
 8. The autoinjector (1) according to claims 3, 5 and 6, wherein the collar (16) abuts the carrier boss (8.4) when the needle shroud (7) is in the first extended position (FEP).
 9. The autoinjector (1) according to claim 8, wherein the collar (16), the needle shroud (7) and the syringe carrier (8) are moved proximally relative to the case (2) when the needle shroud (7) is moved from the first extended position (FEP) to a first retracted position (FRP).
 10. The autoinjector (1) according to claim 8, wherein a proximal end (8.1) of the syringe carrier (8) abuts a proximal end (2.11) of the case (2) when the needle shroud (7) is in the first retracted position (FRP) to provide a feedback.
 11. The autoinjector (1) according to claim 9, wherein the shroud boss (7.1) is proximal of the proximal case boss (2.9) when the needle shroud (7) is in the first retracted position (FRP).
 12. The autoinjector (1) according to claim 11, wherein the syringe carrier (8) is advanced distally when the needle shroud (7) is in a second retracted position (SRP) proximal of the first retracted position (FRP), and the shroud boss (7.1) disengages the carrier opening (8.6).
 13. The autoinjector (1) according to claim 12, wherein, when the shroud boss (7.1) disengages the carrier opening (8.6), the collar (16) pushes the syringe carrier (8) distally until the syringe carrier (8) abuts a front stop (2.8) in the case (2) and the collar (16) disengages the syringe carrier (8) under the biasing force of the control spring (9) and pushes the needle shroud (7) into a second extended position (SEP) relative to the case (2).
 14. The autoinjector (1) according to claim 13, wherein, when the collar (16) disengages the syringe carrier (8), the carrier boss (8.4) disengages the plunger opening (12.1) to release the plunger (12).
 15. The autoinjector (1) according to claim 13, wherein the shroud boss (7.1) abuts a distal case boss (2.10) when the needle shroud (7) is in the second extended position (SEP). 